MUSCARINIC REGULATION OF cAMP IN MOUSE NEUROBLASTOMA

The neurotransmitter acetylcholine regulates cAMP concentrations in mouse neuroblastoma cells (clone NS20). In these cells, the action of acetylcholine appears to be specific: it does not alter basal concentrations of cAMP, but prevents the elevation of cAMP which is mediated by either adenosine or prostaglandin E₁. The receptor for acetylcholine which is involved in this phenomenon has been identified as muscarinic. Pilocarpine and carbamylcholine, but not acetate or choline, will substitute for acetylcholine. Furthermore, the action of 10 μM-carbbamylcholine is blocked by ≥ nM concentrations of atropine, isopropamide or 3-quinuclidinylbenzilate, but not by mM concentrations of d-tubocurarine or hexamethonium. Of eight cholinergic antagonists tested, decamethonium and succinylcholine were the only two which were able to substitute for acetylcholine. These two antagonists are known to cause depolarization of post-synaptic cells. Decamethonium and succinylcholine appear to interact with the same muscarinic receptor, as their actions are also blockèd by low concentrations of 3-quinuclidinylbenzilate. In addition to these two depolarizing antagonists, the ionophores, valinomycin, A23187 and X537A, were also found to prevent elevation of cAMP concentrations. The involvement of specific membrane depolarization as being the active agent by which acetylcholine inhibits elevation of cAMP concentrations is discussed.